Use of spatiotemporal response behavior in sensor arrays to detect analytes in fluids

ABSTRACT

Methods, systems and sensor arrays are provided implementing techniques for detecting an analyte in a fluid. The techniques include providing a sensor array including at least a first sensor and a second sensor in an arrangement having a defined fluid flow path, exposing the sensor array to a fluid including an analyte by introducing the fluid along the fluid flow path, measuring a response for the first sensor and the second sensor, and detecting the presence of the analyte in the fluid based on a spatio-temporal difference between the responses for the first and second sensors.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of and claims priority to U.S.application Ser. No. 09/568,784, filed May 10, 2000 now U.S. Pat. No.6,455,319, which claims the benefit of Provisional Application No.60/133,318, filed May 10, 1999 and Provisional Application No.60/140,027, filed Jun. 16, 1999. Each of these prior applications isincorporated by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

The U.S. Government has certain rights in this invention pursuant toContract No. DAAK60-97-K-9503 administered by the Defense AdvancedResearch Projects Agency (DARPA), and Grant No. DAAG55-97-1-0187administered by the Army Research Office (ARO).

BACKGROUND

The invention relates to sensors and sensor systems for detectinganalytes in fluids.

There is considerable interest in developing sensors that act as analogsof the mammalian olfactory system (Lundstrom et al. (1991) Nature352:47–50; Shurmer and Gardner (1992) Sens. Act. B 8:1–11; Shurmer andGardner (1993) Sens. Act. B 15:32). In practice, most chemical sensorssuffer from some interference by responding to chemical species that arestructurally or chemically similar to the desired analyte. Thisinterference is an inevitable consequence of the “lock” being able tofit a number of imperfect “keys”. Such interferences limit the utilityof such sensors to very specific situations.

Arrays of broadly cross-reactive sensors have been exploited to produceresponse patterns that can be used to fingerprint, classify, and in somecases quantify analytes in fluids. Such arrays have been producedincorporating sensors including heated metal oxide thin film resistors(Gardner et al. (1991) Sens. Act. B4:117–121; Gardner et al. (1992)Sens. Act. B 6:71–75), polymer sorption layers on the surfaces ofacoustic wave resonators (Grate and Abraham (1991) Sens. Act. B3:85–111; Grate et al. (1993) Anal. Chem. 65:1868–1881), arrays ofelectrochemical sensors (Stetter et al. (1986) Anal. Chem. 58:860–866;Stetter et al. (1990) Sens. Act. B 1:43–47; Stetter et al. (1993) Anal.Chem. Acta 284:1–11), conductive polymers or composites that consist ofregions of conductors and regions of insulating organic materials(Pearce et al. (1993) Analyst 118:371–377; Shurmer et al. (1991) Sens.Act. B 4:29–33; Doleman et al. (1998) Anal. Chem. 70:2560–2654; Lonerganet al. Chem. Mater. 1996, 8:2298). Arrays of metal oxide thin filmresistors, typically based on tin oxide (SnO₂) films that have beencoated with various catalysts, yield distinct, diagnostic responses forseveral vapors (Corcoran et al. (1993) Sens. Act. B 15:32–37). Surfaceacoustic wave resonators are extremely sensitive to both mass andacoustic impedance changes of the coatings in array elements. Attemptshave also been made to construct arrays of sensors with conductingorganic polymer elements that have been grown electrochemically throughuse of nominally identical polymer films and coatings. Moreover, Pearceet al., (1993) Analyst 118:371–377, and Gardner et al., (1994) Sensorsand Actuators B 18–19:240–243 describe polypyrrole based sensor arraysfor monitoring beer flavor. Shurmer (1990) U.S. Pat. No. 4,907,441,describes general sensor arrays with particular electrical circuitry.U.S. Pat. No. 4,674,320 describes a single chemoresistive sensor havinga semi-conductive material selected from the group consisting ofphthalocyanine, halogenated phthalocyanine and sulfonatedphthalocyanine, which was used to detect a gas contaminant. Other gassensors have been described by Dogan et al., Synth. Met. 60, 27–30(1993) and Kukla, et al. Films. Sens. Act. B., Chemical 37, 135–140(1996).

Sensor arrays formed from a plurality of composites that consist ofregions of a conductor and regions of an insulating organic material,usually an organic polymer as described in U.S. Pat. No. 5,571,401, havesensitivities that are primarily dictated by the swelling-inducedsorption of a vapor into the composite material, and analytes that sorbto similar extents produce similar swellings and therefore producesimilar detected signals (Doleman, et al., (1998) Proc. Natl. Acad. Sci.U.S.A, 95, 5442–5447).

In these systems, the different responses from an analyte exposure tothe array of sensors is used to identify the analyte. Other propertiesof the devices are designed to insure that otherwise all sensors arenominally equivalent so that the fluid containing the analyte isdelivered to all sensors equally effectively—for example, at the sametemperature—so that only the differences in sensors' response propertiesare being measured.

Although these sensor systems have some usefulness, there remains a needin the art for highly-selective sensor arrays for detecting analytes andresolving the components of complex mixtures.

SUMMARY OF THE INVENTION

The present artificial olfactory systems (or electronic noses) usearrays of many receptors to recognize an odorant. In such aconfiguration, the burden of recognition is not on highly specificreceptors, as in the traditional “lock-and-key” molecular recognitionapproach to chemical sensing, but lies instead on the distributedpattern processing of the olfactory bulb and the brain. The system takesadvantage of the spatio-temporal response differences between nominallyidentical sensors that are located at different positions in a fluidflow pattern.

In general, in one aspect, the invention provides a method of detectingan analyte in a fluid. The method includes providing a sensor arrayincluding at least a first sensor and a second sensor in an arrangementhaving a defined fluid flow path; exposing the sensor array to a fluidincluding an analyte by introducing the fluid along the fluid flow path;measuring a response for the first sensor and the second sensor; anddetecting the presence of the analyte in the fluid based on aspatio-temporal difference between the responses for the first andsecond sensors.

Particular implementations of the invention can include one or more ofthe following features. Detecting the presence of the analyte caninclude generating a spatio-temporal response profile indicative of thepresence of the analyte based on the spatio-temporal difference betweenthe responses for the first and second sensors. The spatio-temporalresponse profile can be derived from time information indicating thedependence of sensor response on time. The first sensor can be exposedto the fluid before the second sensor, such that the response of thesecond sensor is delayed with respect to the response of the firstsensor. The first sensor can be exposed to the fluid before the secondsensor, such that the response of the second sensor is changed inamplitude with respect to the response of the first sensor. The firstsensor can include a sensing material; and the response of the firstsensor can be greater than the response of the second sensor for ananalyte having a high affinity for the sensing material. The first andsecond sensors can be selected and arranged to provide a first delaybetween the response of the first sensor and the response of the secondsensor upon exposure of the sensor array to a fluid including a firstanalyte and a second delay between the response of the first sensor andthe response of the second sensor upon exposure of the sensor array to afluid including a second analyte. Measuring the response can includemeasuring the delay between the response of the first sensor and theresponse of the second sensor, and the spatio-temporal differencebetween the responses for the first and second sensors can be derivedfrom the delay. The method can include characterizing the analyte basedon the spatio-temporal difference between the responses. Exposing thesensor array to the fluid can include introducing the fluid at a varyingflow rate. Generating the spatio-temporal response profile can includegenerating flow information indicating the dependence of sensor responseon flow rate. The sensor array can include a plurality of cross-reactivesensors. The sensor array can include a plurality of sensors selectedfrom the group including surface acoustic wave sensors, quartz crystalresonators, metal oxide sensors, dye-coated fiber optic sensors,dye-impregnated bead arrays, micromachined cantilever arrays, compositeshaving regions of conducting material and regions of insulating organicmaterial, composites having regions of conducting material and regionsof conducting or semiconducting organic material, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, and bulk organic conducting polymeric sensors. The firstand second sensors can include composites having regions of a conductingmaterial and regions of an insulating organic material. The first andsecond sensors can include composites having regions of a conductingmaterial and regions of a conducting organic material. The method caninclude generating a digital representation of the analyte based atleast in part on the responses of the first and second sensors. Themethod can include communicating the digital representation of theanalyte to a remote location for analysis.

In general, in another aspect, the invention provides a system fordetecting an analyte in a fluid. The system includes a sensor arrayincluding at least a first sensor and a second sensor in an arrangementhaving a defined fluid flow path; a measuring apparatus coupled to thesensor array, the measuring apparatus being configured to detect aresponse from the first sensor and the second sensor upon exposure ofthe sensor array to a fluid; and a computer configured to generate dataindicating the presence of the analyte in the fluid based on aspatio-temporal difference between the responses for the first andsecond sensors. Particular implementations of the invention can includeone or more of the following features. The data indicating the presenceof the analyte in the fluid can include a spatio-temporal responseprofile derived from the spatio-temporal difference between theresponses for the first and second sensors. The spatio-temporal responseprofile is derived from time information indicating the dependence ofsensor response on time. The first sensor can occupy a first position inthe arrangement and the second sensor a second position in thearrangement, such that the response of the second sensor is delayed intime with respect to the response of the first sensor upon exposure ofthe sensor array to the fluid. The first sensor can occupy a firstposition in the arrangement and the second sensor a second position inthe arrangement, such that the response of the second sensor is changedin amplitude with respect to the response of the first sensor uponexposure of the sensor array to the fluid. The first sensor can includea sensing material, and the response of the first sensor can be greaterthan the response of the second sensor for an analyte having a highaffinity for the sensing material.

The first and second sensors can be selected and arranged to provide afirst delay between the response of the first sensor and the response ofthe second sensor upon exposure of the sensor array to a fluid includinga first analyte and a second delay between the response of the firstsensor and the response of the second sensor upon exposure of the sensorarray to a fluid including a second analyte. The measuring apparatus canbe configured to measure the delay between the response of the firstsensor and the response of the second sensor; and the spatio-temporaldifference between the responses for the first and second sensors can bederived from the delay. The computer can be configured to characterizethe analyte based on the spatio-temporal difference between theresponses. The system can include a flow controller to introduce thefluid to the sensor array at a varying flow rate. The computer can beconfigured to generate flow information indicating the dependence ofsensor response on flow rate. The sensor array can include a pluralityof cross-reactive sensors. The sensor array can include a plurality ofsensors selected from the group including surface acoustic wave sensors,quartz crystal resonators, metal oxide sensors, dye-coated fiber opticsensors, dye-impregnated bead arrays, micromachined cantilever arrays,composites having regions of conducting material and regions ofinsulating organic material, composites having regions of conductingmaterial and regions of conducting or semiconducting organic material,chemically-sensitive resistor or capacitor films,metal-oxide-semiconductor field effect transistors, and bulk organicconducting polymeric sensors. The first and second sensors can includecomposites having regions of a conducting material and regions of aninsulating organic material. The first and second sensors can includecomposites having regions of a conducting material and regions of aconducting organic material. The computer can be configured to generatea digital representation of the analyte based at least in part on theresponses of the first and second sensors. The system can include acommunications port coupled to the computer for communicating thedigital representation of the analyte to a remote location for analysis.

In general, in still another aspect, the invention provides a system fordetecting an analyte in a fluid. The system includes a sensor arrayincluding a first sensor and a second sensor, a fluid inlet proximate tothe sensor array, and a measuring apparatus connected to the sensorarray. The fluid inlet defines a fluid flow pattern for the introductionof a fluid onto the sensor array, such that the first and second sensorsare located at different locations in the sensor array relative to thefluid flow pattern. The measuring apparatus is configured to detect aresponse from the first sensor and the second sensor upon exposure ofthe sensor array to a fluid. The responses define a spatio-temporaldifference between the responses for the first and second sensors basedon the locations of the sensors relative to the fluid flow pattern.

Particular implementations of the invention can include one or more ofthe following features. The spatio-temporal difference can be derivedfrom time information indicating the dependence of sensor response ontime. The first sensor can occupy a first position relative to the fluidflow pattern and the second sensor a second position relative to thefluid flow pattern, such that the response of the second sensor isdelayed with respect to the response of the first sensor upon exposureof the sensor array to the fluid. The first sensor can occupy a firstposition relative to the fluid flow pattern and the second sensor asecond position relative to the fluid flow pattern, such that theresponse of the second sensor is changed in amplitude with respect tothe response of the first sensor upon exposure of the sensor array tothe fluid. The first sensor can include a sensing material and theresponse of the first sensor can be greater than the response of thesecond sensor for an analyte having a high affinity for the sensingmaterial. The first and second sensors can be selected and arranged toprovide a first delay between the response of the first sensor and theresponse of the second sensor upon exposure of the sensor array to afluid including a first analyte and a second delay between the responseof the first sensor and the response of the second sensor upon exposureof the sensor array to a fluid including a second analyte. The measuringapparatus can be configured to measure the delay between the response ofthe first sensor and the response of the second sensor, and thespatio-temporal difference between the responses for the first andsecond sensors can be derived from the delay. The system can include acomputer configured to characterize the analyte based on thespatio-temporal difference between the responses. The system can includea flow controller to introduce the fluid to the sensor array at avarying flow rate. The measuring apparatus can be configured to measureflow information indicating the dependence of sensor response on flowrate. The sensor array can include a plurality of cross-reactivesensors. The system sensor array can include a plurality of sensorsselected from the group including surface acoustic wave sensors, quartzcrystal resonators, metal oxide sensors, dye-coated fiber optic sensors,dye-impregnated bead arrays, micromachined cantilever arrays, compositeshaving regions of conducting material and regions of insulating organicmaterial, composites having regions of conducting material and regionsof conducting or semiconducting organic material, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, and bulk organic conducting polymeric sensors. The firstand second sensors can include composites having regions of a conductingmaterial and regions of an insulating organic material. The first andsecond sensors can include composites having regions of a conductingmaterial and regions of a conducting organic material. The computer canbe configured to generate a digital representation of the analyte basedat least in part on the responses of the first and second sensors.

In general, in still another aspect, the invention provides a system fordetecting an analyte in a fluid. The system includes a sensor arrayincluding a first sensor and a second sensor; a fluid flow exposing thefirst and second sensors to a fluid, such that the first and secondsensors occupy different locations in the sensor array relative to thefluid flow; and a measuring apparatus connected to the sensor array. Themeasuring apparatus is configured to detect a response from the firstand second sensors upon exposure of the sensor array to the fluid flow.The responses define a spatio-temporal difference based on the locationsof the sensors in the sensor array relative to the fluid flow.

Particular implementations of the invention can include one or more ofthe following features. The spatio-temporal difference can be derivedfrom time information indicating the dependence of sensor response ontime. The first sensor can occupy a first position relative to the fluidflow and the second sensor a second position relative to the fluid flow,such that the response of the second sensor is delayed with respect tothe response of the first sensor upon exposure of the sensor array tothe fluid. The first sensor can occupy a first position relative to thefluid flow and the second sensor occupies a second position relative tothe fluid flow, such that the response of the second sensor is changedin amplitude with respect to the response of the first sensor uponexposure of the sensor array to the fluid. The first sensor can includea sensing material, and the response of the first sensor can be greaterthan the response of the second sensor for an analyte having a highaffinity for the sensing material. The first and second sensors can beselected and arranged to provide a first delay between the response ofthe first sensor and the response of the second sensor upon exposure ofthe sensor array to a fluid including a first analyte and a second delaybetween the response of the first sensor and the response of the secondsensor upon exposure of the sensor array to a fluid including a secondanalyte. The measuring apparatus can be configured to measure the delaybetween the response of the first sensor and the response of the secondsensor, and the spatio-temporal difference between the responses for thefirst and second sensors can be derived from the delay. The system caninclude a computer configured to characterize the analyte based on thespatio-temporal difference between the responses. The system can includea flow controller to vary the rate of the fluid flow. The measuringapparatus can be configured to measure flow information indicating thedependence of sensor response on flow rate. The sensor array can includea plurality of cross-reactive sensors. The sensor array can include aplurality of sensors selected from the group including surface acousticwave sensors, quartz crystal resonators, metal oxide sensors, dye-coatedfiber optic sensors, dye-impregnated bead arrays, micromachinedcantilever arrays, composites having regions of conducting material andregions of insulating organic material, composites having regions ofconducting material and regions of conducting or semiconducting organicmaterial, chemically-sensitive resistor or capacitor films,metal-oxide-semiconductor field effect transistors, and bulk organicconducting polymeric sensors. The first and second sensors can includecomposites having regions of a conducting material and regions of aninsulating organic material. The first and second sensors can includecomposites having regions of a conducting material and regions of aconducting organic material. The computer can be configured to generatea digital representation of the analyte based at least in part on theresponses of the first and second sensors.

In general, in still another aspect, the invention provides a sensorarray for detecting an analyte in a fluid. The sensor array includes asubstrate; a first sensor coupled to the substrate at a first location;and a second sensor coupled to the substrate at a second location, suchthat the first and second sensors occupy different locations in thesensor array relative to a fluid flow path.

Particular implementations of the invention can include one or more ofthe following features. The first sensor can occupy a first positionrelative to the fluid flow path and the second sensor a second positionrelative to the fluid flow path, the first sensor being configured toprovide a first response upon exposure of the sensor array to a fluidand the second sensor being configured to provide a second response uponexposure of the sensor array to the fluid, such that the second responseis delayed with respect to the first response upon exposure of thesensor array to the fluid. The first sensor can provide a firsttime-dependent response upon exposure of the sensor array to a fluid,and the second sensor can provide a second time-dependent response uponexposure of the sensor array to the fluid, the first sensor can occupy afirst position relative to the fluid flow path and the second sensor asecond position relative to the fluid flow path, such that the secondtime-dependent response is changed in amplitude with respect to thefirst time-dependent response upon exposure of the sensor array to thefluid. The first sensor can include a sensing material, and the responseof the first sensor can be greater than the response of the secondsensor for an analyte having a high affinity for the sensing material.The first and second sensors can be selected and arranged to provide afirst delay between a response of the first sensor and a response of thesecond sensor upon exposure of the sensor array to a fluid including afirst analyte and a second delay between a response of the first sensorand a response of the second sensor upon exposure of the sensor array toa fluid including a second analyte. The sensor array can include aplurality of cross-reactive sensors. The sensor array can include aplurality of sensors selected from the group including surface acousticwave sensors, quartz crystal resonators, metal oxide sensors, dye-coatedfiber optic sensors, dye-impregnated bead arrays, micromachinedcantilever arrays, composites having regions of conducting material andregions of insulating organic material, composites having regions ofconducting material and regions of conducting or semiconducting organicmaterial, chemically-sensitive resistor or capacitor films,metal-oxide-semiconductor field effect transistors, and bulk organicconducting polymeric sensors. The first and second sensors can includecomposites having regions of a conducting material and regions of aninsulating organic material. The first and second sensors can includecomposites having regions of a conducting material and regions of aconducting organic material.

Advantages that can be seen in implementations of the invention includeone or more of the following. Taking advantage of a spatio-temporalproperty of a sensor array can impart very useful information on analyteidentification and detection relative to arrays where no spatiotemporalinformation is available because all sensors are nominally in identicalpositions with respect to the fluid flow characteristics and are exposedto the analyte at nominally identical times during the fluid samplingexperiment.

Electronics can be implemented to record the time delay between sensorresponses and to use this information to characterize the analyte ofinterest in the fluid. This mode can also be advantageous because it canallow automatic nulling of any sensor drift, environmental variations(such as temperature, humidity, etc.) and the like. Also, a complex odormixture can be better resolved into its components based on thespatiotemporal characteristics of the array response relative only tothe differences in fingerprints on the various sensors types in thearray. Additionally, these techniques can be used in conjunction withdifferential types of measurements to selectively detect only certainclasses or types of analytes, because the detection can be gated to onlyfocus on signals that exhibit a desired correlation time between theirresponses on the sensors that are in different exposure times relativeto the sensor response on the first sensor that detects an analyte.

BRIEF DESCRIPTION OF THE FIGURES

These and other objects of the present invention will now be describedin detail with reference to the accompanying drawings, in which:

FIG. 1 is a block diagram illustrating a system for detecting an analytein a fluid.

FIG. 2 is a flow diagram illustrating a method of detecting an analytein a fluid.

FIG. 3 illustrates one implementation of a system for detecting ananalyte in a fluid according to the invention.

FIGS. 4 a–b are plots of sensor response as a function of time for thesensor array shown in FIG. 3.

FIGS. 5 a–b are plots of response as a function of flow rate and linearflow rate, respectively, for one sensor in the array shown in FIG. 3.

FIG. 6 is a schematic diagram illustrating an alternate implementationof a system for detecting an analyte in a fluid according to theinvention.

FIG. 7 is a graph illustrating sensor response as a function of sensorposition in an experiment involving the array shown in FIG. 6.

FIG. 8 is a graph illustrating a resistance versus time profilecalculated for a sensor array comprising eight nominally identicalpoly(methyloctadecylsiloxane)-carbon black composite sensors.

FIG. 9 is a graph illustrating a plot of sensor output versus time forthe sensor array of FIG. 8.

FIGS. 10 a–b are graphs illustrating the resistance (delta ppm) behaviorand sensor output as a function of time for a single exposure having thelargest sensor output for the experiment of FIGS. 8 and 9.

FIGS. 10 a–b are graphs illustrating the resistance (delta ppm) behaviorand sensor output as a function of time for a single exposure having anintermediate sensor output for the experiment of FIGS. 8 and 9.

FIGS. 12 a–b are graphs illustrating the resistance (delta ppm) behaviorand sensor output as a function of time for a single exposure having thesmallest sensor output for the experiment of FIGS. 8 and 9.

FIGS. 13 a–b are graphs illustrating the resistance (delta ppm) behaviorand sensor output as a function of time for two “near miss” backgroundwindows for the experiment of FIGS. 8 and 9.

FIGS. 14 a–b are graphs illustrating resistance transients and change inresistance as a function of time showing the dependence of signal from aventilated sensor array on flow rate.

FIGS. 15 a–c are graphs illustrating response transients at varying flowrates; response slope as a function of flow rate through the sensor; andsignal to noise after 5 s exposure as a function of flow rate,respectively, for an experiment involving the ventilated sensor array ofFIGS. 14 a–b.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1 illustrates a system 100 for detecting an analyte in a fluid.System 100 includes a sensor array 110, in which an arrangement of aplurality of sensors 120 defines a fluid channel 130. Optionally, sensorarray 110 is configured to include one or more fluid channels 140 inaddition to fluid channel 130, each fluid channel 140 including anadditional plurality of sensors 150. A fluid to be analyzed, which maybe in gaseous or liquid form, is exposed to sensor array 110 throughfluid inlet 160, for example from fluid reservoir 170. Response signalsfrom the sensors 120, 150 in sensor array 110 resulting from exposure ofthe fluid to the sensor array are received and processed in detector180, which may include, for example, signal-processing electronics, ageneral-purpose programmable digital computer system of conventionalconstruction, or the like.

A method 200 of using system 100 to detect the presence of an analyte ina fluid is illustrated in FIG. 2. A fluid including an analyte isintroduced onto a sensor array 110 (step 210). According to a flowpattern defined by the configuration of array 110 or by the introductionof the fluid, at a time t the fluid interacts with a first sensor orsensors (step 220). Detector 180 detects and records response signalsfrom the first sensor(s) (step 230). The fluid then interacts with asecond sensor or sensors at a time t+δ (step 240), and detector 180detects and records response signals from the second sensor(s) (step250).

Steps 230 and 240 are repeated as the fluid travels across array 110,until each sensor in the array has been exposed to the fluid and thecorresponding response signal recorded by detector 180 (The NO branch ofstep 260). The recorded response signals are then processed to detectand or characterize an analyte or combination of analytes in the fluid(step 270).

Sensors 120, 180 can include any of a variety of known sensors,including, for example, surface acoustic wave sensors, quartz crystalresonators, metal oxide sensors, dye-coated fiber optic sensors,dye-impregnated bead arrays, micromachined cantilever arrays, compositeshaving regions of conducting material and regions of insulating organicmaterial, composites having regions of conducting material and regionsof conducting or semiconducting organic material, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, bulk organic conducting polymeric sensors, and other knownsensor types. Techniques for constructing arrays of such sensors areknown, as disclosed in Harsanyi, G., Polymer Films in SensorApplications (Technomic Publishing Co., Basel, Switzerland, 1995), andU.S. Pat. Nos. 6,017,440, 6,013,229 and 5,911,872 and co-pending U.S.patent application Ser. No. 09/409,644, filed Oct. 1, 1999, which areincorporated by reference herein. Techniques for fabricating particularsensor types are disclosed in Ballantine, D. S.; Rose, S. L.; Grate, J.W.; Wohltjen, H. Anal. Chem. 1986, 58, 3058; Grate, J. W.; Abraham, M.H. Sens. Actuators B 1991, 3, 85; Grate, J. W.; Rosepehrsson, S. L.;Venezky, D. L.; Klusty, M.; Wohltjen, H. Anal. Chem. 1993, 65, 1868;Nakamoto, T.; Fukuda, A.; Moriizumi, T. Sens. Actuators B 1993, 10, 85(surface acoustic wave (SAW) devices), Gardner, J. W.; Shurmer, H. V.;Corcoran, P. Sens. Actuators B 1991, 4, 117; Gardner, J. W.; Shurmer, H.V.; Tan, T. T. Sens. Actuators B 1992, 6, 71; Corcoran, P.; Shurmer, H.V.; Gardner, J. W. Sens. Actuators B 1993, 15, 32 (tin oxide sensors),Shurmer, H. V.; Corcoran, P.; Gardner, J. W. Sens. Actuators B 1991, 4,29; Pearce, T. C.; Gardner, J. W.; Friel, S.; Bartlett, P. N.; Blair, N.Analyst 1993, 118, 371 (conducting organic polymers), Freund, M. S.;Lewis, N. S. Proc. Natl. Acad. Sci 1995, 92, 2652 (materials havingregions of conductors and regions of insulating organic material),White, J.; Kauer, J. S.; Dickinson, T. A.; Walt, D. R. Anal. Chem. 1996,68, 2191 (dye-impregnated polymer films on fiber optic sensors), Butler,M. A.; Ricco, A. J.; Buss, R. J. Electrochem. Soc. 1990, 137, 1325;Hughes, R. C.; Ricco, A. J.; Butler, M. A.; Pfeifer, K. B. J. Biochem.and Biotechnol. 1993, 41, 77 (polymer-coated micromirrors), Slater, J.M.; Paynter, J. Analyst 1994, 119, 191; Slater, J. M.; Watt, E. J.Analyst 1991, 116, 1125 (quartz crystal microbalances (QCMs)), Keyvani,D.; Maclay, J.; Lee, S.; Stetter, J.; Cao, Z. Sens. Actuators B 1991, 5,199 (electrochemical gas sensors), Zubkans, J.; Spetz, A. L.; Sundgren,H.; Winquist, F.; Kleperis, J.; Lusis, A.; Lundstrom, I. Thin SolidFilms 1995, 268, 140 (chemically sensitive field-effect transistors) andLonergan, M. C.; Severin, B. J.; Doleman, B. J.; Beaber, S. A.; Grubbs,R. H.; Lewis, N. S. Chem. Mater. 1996, 8, 2298 carbon black-polymercomposite chemiresistors). Additional sensor array fabricationtechniques are disclosed in Albert, K. J., Lewis, N. S., et al.Cross-Reactive Chemical Sensor Arrays, Chemical Reviews, 2000, 100 (inpress) and the references cited therein.

In one implementation, sensor array 110 incorporates multiple sensingmodalities, for example comprising a spatial arrangement ofcross-reactive sensors 120, 180 selected from known sensor types, suchas those listed above, such that a given analyte elicits a response frommultiple sensors in the array and each sensor responds to many analytes.Preferably, the sensors in the array 110 are broadly cross-reactive,meaning each sensor in the array responds to multiple analytes, and, inturn, each analyte elicits a response from multiple sensors.

Sensor arrays allow expanded utility because the signal for an imperfect“key” in one channel can be recognized through information gathered onanother, chemically or physically dissimilar channel in the array. Adistinct pattern of responses produced over the collection of sensors inthe array can provide a fingerprint that allows classification andidentification of the analyte, whereas such information would not havebeen obtainable by relying on the signals arising solely from a singlesensor or sensing material. By developing an empirical catalogue ofinformation on chemically diverse sensors—made, for example, withvarying ratios of semiconductive, conducting, and insulating componentsand by differing fabrication routes—sensors can be chosen that areappropriate for the analytes expected in a particular application, theirconcentrations, and the desired response times. Further optimization canthen be performed in an iterative fashion as feedback on the performanceof an array under particular conditions becomes available.

The sensor arrays of system 100 provide still further benefits byincorporating spatio-temporal response information that is exploited bydetector 180 to aid in analyte detection and identification. Takingadvantage of a spatio-temporal property of a sensor array can impartuseful information on analyte detection and identification relative toarrays where no spatiotemporal information is available because allsensors are nominally in identical positions with respect to the fluidflow characteristics and are exposed to the analyte at nominallyidentical times during the fluid sampling experiment. Electronics can beimplemented in detector 180 to record a time delay between sensorresponses and to use this information to characterize the analyte ofinterest in the fluid. This mode can also be advantageous because it canallow automatic nulling of any sensor drift, environmental variations(such as temperature, humidity, etc.) and the like. Also, a complexanalyte mixture can be better resolved into its components based on thespatiotemporal characteristics of the array response relative only tothe differences in fingerprints on the various sensors types in thearray. Additionally, the method can be used in conjunction withdifferential types of measurements to selectively detect only certainclasses or types of analytes, because the detection can be gated to onlyfocus on signals that exhibit a desired correlation time between theirresponses on the sensors that are in different exposure times relativeto the sensor response on the first sensor that detects an analyte.

Thus, for example, sensor arrays 110 can be configured such that lowvapor pressure analytes in the gas phase will have a high affinitytowards the sensors and will sorb strongly to them. This strong sorptionproduces a strong response at the first downstream sensor that theanalyte encounters, a weaker response at the second downstream sensor,and a still weaker response at other downstream sensors. Differentanalytes will produce a detectable and useful time delay between theresponse of the first sensor and the response of the other downstreamsensors. As a result, detector 180 can use the differences in responsetime and amplitude to detect and characterize analytes in a carrierfluid, analogous to the use of gas chromatography retention times, whichare well known in the gas chromatography literature and art.

Spatio-temporal information can be obtained from an array of two or moresensors by varying the sensors' exposure to the fluid containing theanalyte across the array (e.g., by generating a spatial and/or temporalgradient across the array), thereby allowing responses to be measuredsimultaneously at various different exposure levels and for variousdifferent sensor compositions. For example, an array 110 of sensors 120,150, can be configured to vary the composition of the sensors in thehorizontal direction across the array, such that sensor composition inthe vertical direction across the array remains constant. One may thencreate a spatio-temporal gradient in the vertical direction across thearray—for example, by introducing the fluid from the top of the arrayand providing for fluid flow vertically down the array, thereby allowingthe simultaneous analysis of chemical analytes at different sensorcompositions and different exposure levels. Similarly, in an array 110including a plurality of different sensors 120, 150 (i.e., an array inwhich each sensor is of a different type or composition),spatio-temporal variation can be introduced by systematically varyingthe flow rate at which the analyte-containing fluid is exposed to thesensors in the array. Again, in this implementation, measuring theresponse of each of the sensors 120, 150 at a variety of different flowrates allows the simultaneous analysis of analytes at different sensorcompositions and different exposure levels.

Thus, in one implementation, the sensors 120, 150 defining each fluidchannel 130, 140 are nominally identical—that is, the sensors 120, 150within a given fluid channel 130, 140 are identical. In contrast, sensorarray 110 incorporates a predetermined inter-sensor variation in thechemistry, structure or composition of the sensors 120, 150 betweenfluid channels 130, 140. The variation may be quantitative and/orqualitative. For example, different channels 130, 140 can be constructedto incorporate sensors of different types, such as incorporating aplurality of nominally identical metal oxide gas sensors in a fluidchannel 130, a plurality of conducting polymer sensors in an adjacentfluid channel 140, and so on across array 110. Alternatively,compositional variation can be introduced by varying the concentrationof a conductive or semiconductive organic material in a composite sensoracross fluid channels. In still another variation, a variety ofdifferent organic materials may be used in sensors in differentchannels. Similar patterns of introducing compositional variation intosensor arrays 110 will be readily apparent to those skilled in the art.

Although FIG. 1 illustrates fluid channels 130, 140 as linear channelsextending in just one direction, sensor arrays can be configured toprovide similar fluid channels having different geometries—for example,arrays with sensors arranged in two or more directions relative to thefluid flow, such as a circular array having a radial arrangement ofsensors around a fluid introduction point. And although sensor array 110has been described as incorporating one or more fluid channels eachcomprising a plurality of nominally identical sensors, those skilled inthe art will recognize that the techniques described herein can be usedto generate useful spatio-temporal information from arrays including aplurality of sensors all of different chemistry, structure orcomposition, with the fluid path being defined by the introduction ofthe fluid onto the array. In this implementation, spatio-temporalresponse data can be generated by introducing the fluid onto the arrayat varying flow rates, for example, by using a flow controller of knownconstruction to systematically vary the rate at which the fluid isintroduced over time. Alternatively, flow rate variation can beintroduced by simply exposing the array to a naturally varying fluidflow, such as a flow of air.

A system 100 is fabricated by electrically coupling the sensor leads ofan array of differently responding sensors to an electrical measuringdevice 180. The device measures changes in signal at each sensor of thearray, preferably simultaneously and preferably over time. The signal isan electrical resistance, impedance or other physical property of thematerial in response to the presence of the analyte in the fluid.Frequently, the device 180 includes signal processing means and is usedin conjunction with a computer and data structure for comparing a givenresponse profile to a structure-response profile database forqualitative and quantitative analysis. Typically an array 110 for use insystem 100 comprises usually at least ten, often at least 100, andperhaps at least 1000 different sensors though with mass depositionfabrication techniques described herein or otherwise known in the art,arrays of on the order of at least one million sensors are readilyproduced.

In one mode of operation with an array of sensors, each sensor providesa first electrical signal when the sensor is contacted with a firstfluid comprising a first chemical analyte, and a second electricalsignal between its conductive leads when the sensor is contacted with asecond fluid comprising a second, different chemical analyte. The fluidsmay be liquid or gaseous in nature. The first and second fluids mayreflect samples from two different environments, a change in theconcentration of an analyte in a fluid sampled at two time points, asample and a negative control, etc. The sensor array necessarilycomprises sensors that respond differently to a change in an analyteconcentration or identity, i.e., the difference between the first andsecond electrical signal of one sensor is different from the differencebetween the first and second electrical signals of another sensor.

In one embodiment, the temporal response of each sensor (for example,signal as a function of time) is recorded. The temporal response of eachsensor can be normalized to a maximum percent increase and percentdecrease in signal that produces a response pattern associated with theexposure of the analyte. By iterative profiling of known analytes, astructure-function database correlating analytes and response profilesis generated. Unknown analytes can then be characterized or identifiedusing response pattern comparison and recognition algorithms.Accordingly, analyte detection systems comprising sensor arrays, anelectrical measuring device for detecting signal at each sensor, acomputer, a data structure of sensor array response profiles, and acomparison algorithm are provided. In another embodiment, the electricalmeasuring device is an integrated circuit comprising neuralnetwork-based hardware and a digital-analog converter (DAC) multiplexedto each sensor, or a plurality of DACs, each connected to differentsensor(s).

The desired signals if monitored as dc electrical resistances for thevarious sensor elements in an array can be read merely by imposing aconstant current source through the resistors and then monitoring thevoltage across each resistor through use of a commercial multiplexable20 bit analog-to-digital converter. Such signals are readily stored in acomputer that contains a resident algorithm for data analysis andarchiving. Signals can also be preprocessed either in digital or analogform; the latter might adopt a resistive grid configuration, forexample, to achieve local gain control. In addition, long timeadaptation electronics can be added or the data can be processeddigitally after it is collected from the sensors themselves. Thisprocessing could be on the same chip as the sensors but also couldreside on a physically separate chip or computer.

Data analysis can be performed using standard chemometric methods suchas principal component analysis and SIMCA, which are available incommercial software packages that run on a PC or which are easilytransferred into a computer running a resident algorithm or onto asignal analysis chip either integrated onto, or working in conjunctionwith, the sensor measurement electronics. The Fisher linear discriminantis one preferred algorithm for analysis of the data, as described below.In addition, more sophisticated algorithms and supervised orunsupervised neural network based learning/training methods can beapplied as well (Duda, R. O.; Hart, P. E. Pattern Classification andScene Analysis; John Wiley & Sons: New York, 1973, pp 482).

The signals can also be useful in forming a digitally transmittablerepresentation of an analyte in a fluid. Such signals could betransmitted over the Internet in encrypted or in publicly available formand analyzed by a central processing unit at a remote site, and/orarchived for compilation of a data set that could be mined to determine,for example, changes with respect to historical mean “normal” values ofthe breathing air in confined spaces, of human breath profiles, and of avariety of other long term monitoring situations where detection ofanalytes in fluids is an important value-added component of the data.

An array of 20–30 different sensors is sufficient for many analyteclassification tasks but larger array sizes can be implemented as well.Temperature and humidity can be controlled but because a preferred modeis to record changes relative to the ambient baseline condition, andbecause the patterns for a particular type and concentration of odorantare generally independent of such baseline conditions, it is notcritical to actively control these variables in some implementations ofthe technology. Such control could be achieved either in open-loop orclosed-loop configurations.

The sensor arrays disclosed herein could be used with or withoutpreconcentration of the analyte depending on the power levels and othersystem constraints demanded by the user. Regardless of the samplingmode, the characteristic patterns (both from amplitude and temporalfeatures, depending on the most robust classification algorithm for thepurpose) associated with certain disease states and other volatileanalyte signatures can be identified using the sensors disclosed herein.These patterns are then stored in a library, and matched against thesignatures emanating from the sample to determine the likelihood of aparticular odor falling into the category of concern (disease ornondisease, toxic or nontoxic chemical, good or bad polymer samples,fresh or old fish, fresh or contaminated air etc.).

Analyte sampling will occur differently in the various applicationscenarios. For some applications, direct headspace samples can becollected using either single breath and urine samples in the case ofsampling a patients breath for the purpose of disease or health statedifferentiation and classification. In addition, extended breathsamples, passed over a Tenax, Carbopack, Poropak, Carbosieve, or othersorbent preconcentrator material, can be obtained when needed to obtainrobust intensity signals. The absorbent material of the fluidconcentrator can be, but is not limited to, a nanoporous material, amicroporous material, a chemically reactive material, a nonporousmaterial and combinations thereof. In certain instances, the absorbentmaterial can concentrate the analyte by a factor that exceeds a factorof about 10⁵, or by a factor of about 10² to about 10⁴. In anotherembodiment, removal of background water vapor is conducted inconjunction, such as concomitantly, with the concentration of theanalyte. Once the analyte is concentrated, it can be desorbed using avariety of techniques, such as heating, purging, stripping, pressuringor a combination thereof.

Breath samples can be collected through a straw or suitable tube in apatient's mouth that is connected to the sample chamber (orpreconcentrator chamber), with the analyte outlet available for captureto enable subsequent GC/MS or other selected laboratory analyticalstudies of the sample. In other applications, headspace samples ofodorous specimens can be analyzed and/or carrier gases can be used totransmit the analyte of concern to the sensors to produce the desiredresponse. In still other cases, the analyte will be in a liquid phaseand the liquid phase will be directly exposed to the sensors; in othercases the analyte will undergo some separation initially and in yetother cases only the headspace of the analyte will be exposed to thesensors.

Using the device of the present invention, the analyte can beconcentrated from an initial sample volume of about 10 liters and thendesorbed into a concentrated volume of about 10 milliliters or less,before being presented to the sensor array.

Suitable commercially available adsorbent materials include but are notlimited to, Tenax TA, Tenax GR, Carbotrap, Carbopack B and C, CarbotrapC. Carboxen, Carbosieve SIII, Porapak, Spherocarb, and combinationsthereof. Preferred adsorbent combinations include, but are not limitedto, Tenax GR and Carbopack B; Carbopack B and Carbosieve SIII; andCarbopack C and Carbopack B and Carbosieve SIII or Carboxen 1000. Thoseskilled in the art will know of other suitable absorbent materials.

In another embodiment, removal of background water vapor is conducted inconjunction, such as concomitantly, with the concentration of theanalyte. Once the analyte is concentrated, it can be desorbed using avariety of techniques, such as heating, purging, stripping, pressuringor a combination thereof. In these embodiments, the sample concentratoris wrapped with a wire through which current can be applied to heat andthus, desorb the concentrated analyte. The analyte is thereaftertransferred to the sensor array.

In some cases, the array will not yield a distinct signature of eachindividual analyte in a region, unless one specific type of analytedominates the chemical composition of a sample. Instead, a pattern thatis a composite, with certain characteristic temporal features of thesensor responses that aid in formulating a unique relationship betweenthe detected analyte contents and the resulting array response, will beobtained.

In a preferred embodiment of signal processing, the Fisher lineardiscriminant searches for the projection vector, w, in the detectorspace that maximizes the pairwise resolution factor, i.e., rf, for eachset of analytes, and reports the value of rf along this optimal lineardiscriminant vector. The rf value is an inherent property of the dataset and does not depend on whether principal component space or originaldetector space is used to analyze the response data. This resolutionfactor is basically a multi-dimensional analogue to the separationfactors used to quantify the resolving power of a column in gaschromatography, and thus the rf value serves as a quantitativeindication of how distinct two patterns are from each other, consideringboth the signals and the distribution of responses upon exposure to theanalytes that comprise the solvent pair of concern. For example,assuming a Gaussian distribution relative to the mean value of the datapoints that are obtained from the responses of the array to any givenanalyte, the probabilities of correctly identifying an analyte as a or bfrom a single presentation when a and b are separated with resolutionfactors of 1.0, 2.0 or 3.0 are approximately 76%, 92% and 98%respectively.

To compute the rf, from standard vector analysis, the mean responsevector, x_(a), of an n-sensor array to analyte a is given as then-dimensional vector containing the mean autoscaled response of eachsensors, A_(sj), to the a^(th) analyte as components such thatx _(a)=(A _(a1) , A _(a2) , . . . A _(an))The average separation, |d|, between the two analytes, a and b, in theEuclidean sensor response space is then equal to the magnitude of thedifference between x_(a) and x_(b). The noise of the sensor responses isalso important in quantifying the resolving power of the sensor array.Thus the standard deviations, s_(a,d) and s_(b,d), obtained from all theindividual array responses to each of a and b along the vector d, areused to describe the average separation and ultimately to define thepairwise resolution factor asrf=d _(w)/√(σ² _(a,w)+σ² _(b,w)).

Even if the dimensionality of odor space is fairly small, say on theorder of 10¹, there is still interest in being able to model thebiological olfactory system in its construction of arrays consisting oflarge numbers of receptor sites. Furthermore, even if a relatively smallnumber (<10) of ideal sensors could indeed span odor space, it is notlikely that such ideal sensors could be identified. In practice,correlations between the elements of a sensor array will necessitate amuch larger number of sensors to successfully distinguish molecules.Furthermore, performance issues such as response time, signal averaging,or calibration ranges may require multiple sensors based on eachmaterial. Analysis of regions will add additional degrees of freedom ifthe components of the region are to be individually identified and willrequire large numbers of sensors. Fabrication of large numbers ofsensors also enables the use of very powerful coherent signal detectionalgorithms to pull a known, but small amplitude, signal, out of a noisybackground. Because of all of these issues, the number of sensorsrequired to successfully span odor space in a practical device mayrapidly multiply from the minimum value defined by the dimensionality ofsmell space.

The sensor arrays disclosed herein act as “electronic noses” to offerease of use, speed, and identification of analytes and/or analyteregions all in a portable, relatively inexpensive implementation. A widevariety of analytes and fluids may be analyzed by the disclosed arraysso long as the subject analyte is capable generating a differentialresponse across a plurality of sensors of the array. Analyteapplications include broad ranges of chemical classes such as organicsincluding, for example, alkanes, alkenes, alkynes, dienes, alicyclichydrocarbons, arenes, alcohols, ethers, ketones, aldehydes, carbonyls,carbanions, biogenic amines, thiols, polynuclear aromatics andderivatives of such organics, e.g., halide derivatives, etc.,biomolecules such as sugars, isoprenes and isoprenoids, fatty acids andderivatives, etc.

Commercial applications of the arrays include environmental toxicologyand remediation, materials quality control, food and agriculturalproducts monitoring, fruit ripening control, fermentation processmonitoring and control applications, flavor composition andidentification, cosmetic/perfume/fragrance formulation, anaestheticdetection, ambient air quality monitoring, emissions monitoring andcontrol, leak detection and identification, H₂S monitoring, automobileoil or radiator fluid monitoring, hazardous spill identification,fugitive emission identification, medical diagnostics, detection andclassification of bacteria and microorganisms both in vitro and in vivofor biomedical uses and medical diagnostic uses, infectious diseasedetection, body fluids analysis, drug discovery, telesurgery, breathalcohol analyzers, illegal substance detection and identification, arsoninvestigation, smoke and fire detection, combustible gas detection,explosives and chemical weapons detection and identification, enclosedspace surveying, personal identification, automatic ventilation controlapplications (cooking, smoking, etc.), air intake monitoring, and thelike.

The following examples are offered by way of illustration and not by wayof limitation.

EXAMPLES

In the following examples, broadly responsive sensor arrays wereconstructed based on carbon black composites for various vapor detectiontasks. Individual sensor elements were constructed from films consistingof carbon black particles dispersed into insulating organic polymers.The carbon black endows electrical conductivity to the films, whereasthe different organic polymers are the source of chemical diversitybetween elements in the sensor array. Swelling of the polymer uponexposure to a vapor increases the resistance of the film, therebyproviding an extraordinarily simple means for monitoring the presence ofa vapor. Because different polymer compositions are present on eachsensor element, an array of elements responds to a wide variety ofvapors (or complex mixtures of vapors) in a distinctive, identifiablefashion. The electrical resistance signals that are output from thearray can be readily integrated into software- or hardware-baseddecision systems, allowing for an integration of sensing and analysisfunctions into a compact, low-power, simple vapor sensor.

Preparation of Sensor Arrays.

In general, arrays of nominally identical polymer-carbon black compositesensors were constructed by spray-coating a ceramic substrate havingpairs of leads spaced 1.0 mm apart. Each sensor was sprayed from asuspension of carbon black in a solvent that dissolved the polymer, andthe components had a weight percentage of 20% of carbon black todissolved polymer. The leads were 3.5 mm in length and 0.1 mm in widthand were interdigitated such that the total width contacting a givensensor film was 3.0 mm. The output of every pair of leads from eachsensor were connected to a printed circuit board equipped withelectronics that read the resistance signals to a precision of <5 ppmevery 0.5 s on the entire bank of sensors.

Example 1

Referring to FIG. 3, an array 300 of eight nominally identicalpoly(methyloctadecylsiloxane)-carbon black composite sensors 301–308 wasconstructed as described above. A stream 310 of 2,4-dinitrotoluene (DNT)in air at 5% of its vapor pressure was directed onto the surface, suchthat the stream was directed at sensor 304 and then moved radially inboth directions across the array.

5% of the vapor pressure of DNT at 20° C. was selected as a dilution ofDNT that would deliver less than 10 ppb of the compound to the sensors.The DNT source was a tube approximately a meter in length that heldabout 180 g of loosely packed, granulated DNT. The air flow through thetube was 0.5 L-min⁻¹. This air flow was mixed with, and thereforediluted by a flow of 9.5 L-min⁻¹ of air (from the same source) that didnot flow through the DNT tube. At this dilution, the upper limit of theDNT concentration is 7 ppb, because the vapor pressure of DNT at roomtemperature is approximately 140 ppb. If saturation of the backgroundair through the DNT tube occurred, and if no DNT stuck to the walls ofthe tubing after mixing with the pure background analyte flow, thisdilution would produce a concentration of 7 ppb of DNT. However,analyses performed by sorbing the analyte flow onto Tenax for a 10minute period (to obtain enough DNT with which to perform analysis) andthen analyzing the desorbed products with a GC-ECD system indicated thatthe actual DNT concentration exiting the tubing and available to bedetected was approximately 0.2–0.4 ppb.

Flows were controlled by mass flow controllers in a computer controlledsystem that has been described in detail in Severin, E. J., Doleman, B.J., Lewis, N. S., Anal. Chem., 2000, 72, 658. A union-T was used to mixthe background and analyte-containing gases, and a short Teflon tube wasconnected to the output of the union to direct the gas toward the bankof sensors. The array substrate was placed such that the sensors wereperpendicular to the output of the DNT flow and were approximately 0.5cm from the end of the tubing.

The DNT flow was delivered at four flow rates: 0.5 liters/min, 1.0liters/min, 3.0 liters/min and 6.0 liters/min. Results reporting thesensor response as a function of time for the eight sensors are plottedin FIGS. 4 a–b. Sensor 304, in the center of the array and directlyunder the flow, responds faster and to a greater extent for each of thetested flow rates. The flow rate dependence of the response for thissensor is illustrated in FIGS. 5 a–b, which depict the slope of theresponse for sensor 304 as a function of flow rate.

Example 2

Referring to FIG. 6, an array 600 of eight nominally identicalpoly(ethylene-co-vinylacetate)-carbon black composite sensors 601–608was prepared in a row on a single ceramic substrate as described above.An aluminum plate 610 was placed over the substrate, separated from thesubstrate surface by narrow Teflon spacers to create a small channelapproximately 5 mm wide and 70 microns high over the row of sensors,with openings 615, 620 at either end. The substrate assembly was placedin a Teflon chamber 630 of dimensions approximately 5 cm by 5 cm by 10cm. A stream of air was directed through the Teflon chamber. Flows werecontrolled as described in Severin, E. J., Doleman, B. J., Lewis, N. S.,Anal. Chem., 2000, 72, 658. During times of exposure, this stream alsocontained one of the four analytes at 5% of its vapor pressure. Fouranalytes covering a range of vapor pressures were used to study theresponse characteristics: n-dodecane, n-nonane, methanol, and n-hexane.The total flow into the chamber was maintained constant at all times.

The ΔR/R response was calculated using data averaged over five secondperiods. The baseline resistance, R, was taken from the periodimmediately before starting the vapor presentation and the value of ΔR/Rwas taken as the difference in resistance after 300 seconds of vaporpresentation and the baseline resistance. This response was calculatedfor each of the eight sensor positions.

The spatial dependence of sensor responses to these analytes at each ofthe eight sensors is shown in FIG. 7.

The high vapor pressure analytes produced equilibrium responses ofsimilar magnitude on all of the sensors. By contrast, the lower vaporpressure analytes (n-nonane and n-dodecane) produced higher magnituderesponses on the sensors near the openings than on the sensors in themiddle of the channel.

Example 3

An array 300 of eight nominally identicalpoly(methyloctadecylsiloxane)-carbon black composite sensors 301–308 wasconstructed as described above and configured as described in Example 1.

The experimental protocol consisted of one hour of exposure to air only,followed by ten control exposures to 5 s DNT pulses spaced every 605 s,followed by a randomized sequence of 20 exposures/nonexposures to DNTspaced every 605 s. The data were then analyzed independently withoutknowledge of the actual order of the randomized sequence ofexposures/nonexposures.

A run was also performed to investigate whether responses would beobtained due to small changes in the flow rate of gas to the sensors.For this experiment, the existing lines were unhooked at the outlets ofboth mass flow controllers (the one feeding the DNT generator and theone providing diluent air). The lines were then replaced with lines anda union-T that had never been exposed to DNT or to solvents. The lengthsof the flow paths with the new lines in place approximated those in theDNT dilution system. A run of four 60 s exposures, each separated by 10min, was performed. In this run, 5% of the air during each exposure camevia the mass flow controller that was normally used to feed the DNTgenerator. The total flow rate at all times was 10 L-min⁻¹.

FIG. 8 shows the resistance (in units of 10 kΩ) versus time profilecomputed by averaging over the bank of eight nominally identicalpoly(methyloctadecylsiloxane)-carbon black sensors that were placedperpendicular to the outlet of the DNT flow. The vertical lines show theground truth of when the DNT puffs were applied. The first ten linesrepresent the control set. Note that the time axis spans over 6 hours(22,000 s). The series of “bumps” that are visible on this long timescale plot are not related to the DNT pulses, and in fact representenvironmentally-induced oscillations in the baseline resistance of thesensor. The DNT-induced behavior occurs on a 5 second time scale that isnot discernible on this plot.

FIG. 9 plots sensor output versus time over the 6+ hours of theexperiment. The vertical lines show the ground truth of when DNT puffswere applied. The units on the y-axis are in standard deviations of thesignal relative to the local background of the sensor. As shown in FIG.9, using essentially a matched filter algorithm with adaptive backgroundsubtraction, all DNT exposures and non-exposures were correctlyidentified within the randomized sequence. The black circles show localmaxima of the sensor output that exceeded a given threshold. Based onthis selection criterion, all of the DNT exposures were detected with nofalse alarms. In fact, a much stronger result was obtained: theseparability at the sensor output was sufficient for all DNT exposures.(in the control set and the randomized set) to be correctly identifiedwith zero false alarms over the entire >6 hour duration of theexperiment.

The highest sensor output value (15.3) occurred at the 6th controlsample. The resistance versus time profile for this sample is shown indetail in FIG. 10 a. The sensor output versus time is shown in FIG. 10b. An intermediate case (roughly the median in sensor output fidelity)occurred at the 4th control sample. The resistance versus time profilefor this sample is shown in detail in FIG. 11 a. The sensor outputversus time is shown in FIG. 11 b. The lowest sensor output value (7.35)occurred at the 7th control sample. The resistance versus time profilefor this sample is shown in detail in FIG. 12 a. The sensor outputversus time is shown in FIG. 12 b.

Although all the DNT exposures were perfectly separated from thebackground with zero false alarms, it is interesting to look at the“close calls” or “near false alarms”. In FIG. 9 there are 4 places wherethe sensor output on the background exceeds a threshold of 5 but isstill well below the minimum target value of 7.35. The detailedresistance versus time profiles for 2 of these 4 “near false alarms” areshown in FIGS. 13 a–b.

Example 4

A separate set of experiments was performed to evaluate the dependenceof DNT detection on the flow rate of DNT to the sensors. For this run, apoly(methyloctadecylsiloxane)-carbon black mixture was spray-coated ontothe edges of glass slides. Prior to the deposition of the sensor film,conductive coatings had been deposited onto both surfaces of the slides.Spacers were then placed between these edge-coated slides. The resultwas a sensor with a width of ≈6 mm that had slits 0.13–0.25 mm in widthspanning the length of the sensor. This ventilated sensor assembly wasthen cemented into one end of a section of vacuum hose. The other end ofthe hose was connected to a vacuum pump. A flow meter was placed in theline to monitor the flow rate through the slits in the sensor. Therectangular sensor face was fitted into a similarly-sized aperture in aTeflon block, the fit being loose enough that gas flow onto the sensorcould escape around the edges. The output tube of the gas mixer wasfitted to a second teflon block that was bolted to the block holding thesensor assembly, creating a small chamber with a volume of about 0.3cm³. The resulting distance between the gas mixture outlet and thesensor was 5 mm. The resistance of the sensor was measured by connectingthe leads to one channel in a data acquisition board that recorded theresistance versus time data. The data were then transferred to a laptopcomputer.

Four trials were performed, with each trial using vapor emerging fromthe DNT-containing analyte tube diluted to 5% by volume with backgroundair. In experiment 1, 10 exposures were made following a 20 min purgewith air at 10 L-min⁻¹. Each DNT exposure was 10 s in length. The totalflow rates into the sensor chamber were varied progressively, startingat 1 L-min⁻¹ for the first exposure and ending with an exposure at 10L-min. Each exposure was followed by a purge at 10 L-min⁻¹ of backgroundair. Prior to each exposure, the flow through the vacuum line drawinggas through the sensor was set to produce a flow rate that was 1 L-min⁻¹less than the flow rate impinging onto the sensor chamber. This positivedifferential flow rate arrangement was used to avoid drawing in ambientair through the remaining gap between the sensor and the walls of thechamber.

In experiment 2, 10 exposures were made using the same ascending seriesof total flow rates into the chamber (i.e. 1–10 L-min⁻¹), but no vacuumwas applied during any of the exposures.

In experiment 3, the same ascending series of flow rates into thechamber was used, and the same ascending series of vacuum-induced flowrates through the sensor as in experiment 1 was employed, but no analyte(DNT) was present.

In experiment 4, the flow rate of DNT (at 5% of its vapor pressure at20° C.) into the chamber as not varied, being maintained at 10 L-min⁻¹for all 10 exposures. Vacuum-induced flow rates through the sensor were,however, varied in the same way as in experiments 1 and 3, beginningwith no flow for the first exposure and ending with 9 L-min⁻¹ during the10^(th) and final exposure.

FIGS. 14 a–b illustrates the dependence of signal from the ventilatedsensor on flow rate with the flow rate varying from 1 to 10 liters/min.FIG. 14 a shows resistance transients for a 1 minute exposure of DNT at5% of its vapor pressure (top: vacuum on; bottom: vacuum off). FIG. 14 bshows the change in resistance as a function of time indicatingmagnitude of slope during exposure. As these figures illustrate, pullinganalyte through the sensor at a rate about 1 L-min⁻¹ less than the flowrate of gas into the chamber generally resulted in an increase in sensorresponse of a factor of 2. This was particularly noticeable at higherflow rates. When flow into the sensor chamber was kept at a constant,high rate (10 L-min⁻¹), the sensor response increased, apparently due toincreased flow through the sensor slits.

The ventilated sensor response characteristics for 5 s exposures to 10L-min⁻¹ total flow rates of 5% DNT as a function of flow rate throughthe sensor are illustrated in FIGS. 15 a–c. FIG. 15 a shows responsetransients ranging from no flow through the sensor (second from thebottom) to 9 L-min⁻¹ through the sensor (top). FIG. 15 b shows responseslope as a function of flow rate through the sensor. FIG. 15 c showssignal to noise after 5 s exposure as a function of flow rate.

Although only a few embodiments have been described in detail above,those having ordinary skill in the art will certainly understand thatmany modifications are possible in the preferred embodiment withoutdeparting from the teachings thereof. All such modifications areintended to be encompassed within the following claims.

1. A system for identifying an analyte in a fluid, comprising: a fluidflow chamber having a first end and a second end; a sensor arrayincluding at least a first sensor and a second sensor in an arrangementin the fluid flow chamber such that at least the first sensor isproximal to the first end of the flow chamber and at least the secondsensor is proximal to the second end of the flow chamber thereby havinga defined fluid flow path, wherein a fluid moving in the fluid flowchamber contacts the at least two sensors at different times, each ofthe first and second sensors comprising a sensing area comprisingregions of a conductive material and an organic material; a measuringapparatus coupled to the sensor array, the measuring apparatus beingconfigured to detect a response from the first sensor and the secondsensor upon exposure of the sensor array to the fluid; and a computerconfigured to generate data indicating the analyte in the fluid based ona spatio-temporal difference between the responses for the first andsecond sensors and identifying the analyte based upon thespatio-temporal difference.
 2. The system of claim 1, wherein the dataincludes a spatio-temporal response profile derived from thespatio-temporal difference between the responses for the at least firstand second sensors.
 3. The system of claim 2, wherein thespatio-temporal response profile is derived from time informationindicating the dependence of sensor response on time.
 4. The system ofclaim 3, wherein the first sensor occupies a first position in thearrangement and the second sensor occupies a second position in thearrangement, such that the response of the second sensor is delayed intime with respect to the response of the first sensor upon exposure ofthe sensor array to the fluid.
 5. The system of claim 3, wherein thefirst sensor occupies a first position in the arrangement and the secondsensor occupies a second position in the arrangement, such that theresponse of the second sensor is changed in amplitude with respect tothe response of the first sensor upon exposure of the sensor array tothe fluid.
 6. The system of claim 5, wherein the first sensor includes asensing material; and the response of the first sensor is greater thanthe response of the second sensor for an analyte having a high affinityfor the sensing material.
 7. The system of claim 4, wherein the firstand second sensors are selected and arranged to provide a first delaybetween the response of the first sensor and the response of the secondsensor upon exposure of the sensor array to a fluid including a firstanalyte and a second delay between the response of the first sensor andthe response of the second sensor upon exposure of the sensor array to afluid including a second analyte.
 8. The system of claim 7, wherein: themeasuring apparatus is configured to measure the delay between theresponse of the first sensor and the response of the second sensor; andthe spatio-temporal difference between the responses for the first andsecond sensors is derived from the delay.
 9. The system of claim 8,wherein the computer is configured to characterize the analyte based onthe spatio-temporal difference between the responses.
 10. The system ofclaim 2, further comprising: a flow controller to introduce the fluid tothe sensor array at a varying flow rate.
 11. The system of claim 10wherein the computer is configured to generate flow informationindicating the dependence of sensor response on flow rate.
 12. Thesystem of claim 2, wherein the sensor array includes a plurality ofcross-reactive sensors.
 13. The system of claim 2, wherein the sensorarray further comprises a plurality of sensors selected from the groupincluding surface acoustic wave sensors, quartz crystal resonators,metal oxide sensors, dye-coated fiber optic sensors, dye-impregnatedbead arrays, micromachined cantilever arrays, chemically-sensitiveresistor or capacitor films, metal-oxide-semiconductor field effecttransistors, and bulk organic conducting polymeric sensors.
 14. Thesystem of claim 2, wherein the first and second sensors comprisecomposites having regions of a conducting material and regions of aninsulating organic material.
 15. The system of claim 2, wherein thefirst and second sensors comprise composites having regions of aconducting material and regions of a conducting organic material. 16.The system of claim 2, wherein the computer is configured to generate adigital representation of the analyte based at least in part on theresponses of the first and second sensors.
 17. The system of claim 16,further comprising: a communications port coupled to the computer forcommunicating the digital representation of the analyte to a remotelocation for analysis.
 18. The system of claim 1, wherein the organicmaterial is an insulator.
 19. The system of claim 1, wherein the organicmaterial is a conductor.
 20. The system of claim 1, wherein theconductive material is carbon black.